Chair: Ali Jawaid (Łukasiewicz – PORT, Wroclaw, Poland)

Symposium 2: Neurobiology of Early Life Adversity Across the Lifespan and Across Generations

Adverse or stressful conditions, especially early in life, can have detrimental consequences for adult mental health, with some effects even passing to future generations. This symposium aims to convene a diverse group of leading and emerging neuroscientists to explore the neurobiological roots of these effects including their intergenerational transmission.


Prof. Dr. Mathias Schmidt, MPI Munich, Munich, Germany

Sex-specific consequences of early life adversity: From transcriptome to complex behavior

Early-life stress (ELS) can profoundly shape adult physiology and behavior, leading to resilience or vulnerability to psychopathology. Using rodent models, we employ deep phenotyping methods, such as machine-learning assisted behavioral monitoring with DeepOF, to identify enduring behavioral consequences of ELS that significantly impact the animals’ fitness and health. These behaviors, including complex social behaviors, are linked to alterations in neuronal activation, physiology, transcriptome, and metabolome. Notably, we observe pronounced sex differences in both the behavioral and physiological outcomes of ELS, as well as in the underlying molecular mechanisms. Our findings underscore the importance of developing sex-specific treatment interventions to enhance individual stress resilience and provide effective therapeutic approaches.

References:
1. Brix LM, et al. Metabolic effects of early life stress and pre-pregnancy obesity are long lasting and sex specific in mice. Eur J Neurosci., 2023.
doi: 10.1111/ejn.16047


Prof. Dr. Aniko Korosi, University of Amsterdam, Amsterdam, Netherlands

Long-term effects of early-life stress on cognition and emotional functions: a synergistic action of stress, inflammation and nutrition

Early-life stress is associated with increased vulnerability to cognitive impairments later in life. We investigate the role of a synergistic effect of stress, metabolic factors, nutrition and the neuroimmune system in this early-life induced programming. Using a model where mice face limited nesting material during first post-natal week, we analyze long-term brain effects under both normal and challenging conditions (e.g., LPS, amyloid in Alzheimer’s models, and exercise). We also explore cognitive, emotional functions, neurogenesis, and microglial responses, focusing on essential nutrients like fatty acids and polyphenols as protective interventions. Our findings reveal an impairment of hippocampal neurogenesis and priming of microglia for exaggerated inflammatory responses by ELS. Early dietary intervention can partly mitigate these effects, offering insights for targeted nutrition in vulnerable populations.

References:
1. Reemst K, et al. Molecular underpinnings of programming by early-life stress and the protective effects of early dietary ω6/ω3 ratio, basally and in response to LPS: Integrated mRNA-miRNAs approach. Brain Behav Immun., 2024. doi: 10.1016/j.bbi.2024.01.011
2. Kotah JM, et al. Early-life stress and amyloidosis in mice share pathogenic pathways involving synaptic mitochondria and lipid metabolism. Alzheimers Dement., 2024. doi: 10.1002/alz.13569


Dr. Ali Jawaid, Polish Centre for Technology Development, Łukasiewicz-PORT, Wrocław, Poland

Towards the biological plausibility and biomarkers of intergenerational trauma in humans

Childhood trauma is a major risk factor for adult psychiatric and physical disorders, with recent research indicating these effects may extend across generations. We investigate the molecular basis of the long-term effects and intergenerational transmission of trauma. We examine small non-coding RNAs in serum, sperm, and milk from diverse trauma-exposed cohorts, including Pakistani children and men with histories of complex childhood trauma, Polish mothers with exposure to adverse childhood experiences, and Bosnian adults who were exposed to the genocide during their childhood. Using a parallel mouse model of post-natal trauma involving unpredictable maternal separation and stress, our findings suggest that lipid related circulating microRNAs play a critical role in trauma transmission across generations, highlighting their potential as biomarkers and providing insights into therapeutic strategies.

References:
1. Tomszewska W, et al. Differential microRNAs and metabolites in the breast milk of mothers with adverse childhood experiences correlate with offspring temperament. (In review: Translational Psychiatry)
2. Jawaid A, et al. miRNA differentially expressed in human serum and sperm after childhood trauma potentially impact offspring health. (In revision: Biological Psychiatry)


Weronika Tomaszewska, Nencki Institute of Experimental Biology and Łukasiewicz-PORT, Wrocław, Poland

Interplay of serum lipids and microglia in the susceptibility to the long-term behavioral effects of adverse childhood experiences

Adverse childhood experiences (ACE) significantly increase the risk of adult-onset neuropsychiatric disorders. However, the mechanisms underlying susceptibility versus resilience to the long-term effects of ACE remain largely unknown. We hypothesize that microglia centrally integrate lipid-mediated signals and alter their inflammatory and phagocytic outputs to determine the susceptibility vs. resilience to ACE. Synergizing in vitro analyses of microglia incubated with samples from human ACE cohorts in Pakistan and Bosnia, we demonstrate that microglial metabolism and phagocytosis of healthy synapses are differentially regulated upon stimulation with serum from resilient vs. susceptible individuals. Our ongoing investigations focus on dissecting the individual contribution of peripheral lipids and their associated non-coding RNAs in alteration of microglial functions to determine susceptibility vs. resilience to ACE.

References:
1. https://www.neuron-eranet.eu/projects/MUSE+ACE/

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